Bs Ko

Large genomic rearrangement of BRCA1 and BRCA2 genes in familial breast cancer patients in Korea.

We screened large genomic rearrangements of the BRCA1 and BRCA2 genes in Korean, familial breast cancer patients. Multiplex ligation-dependent probe amplification assay was used to identify BRCA1 and BRCA2 genomic rearrangements in 226 Korean familial breast cancer patients with risk factors for BRCA1 and BRCA2 mutations, who previously tested negative for point mutations in the two genes. We identified only one large deletion (c.4186-1593_4676-1465del) in BRCA1. No large rearrangements were found in BRCA2. Our result indicates that large genomic rearrangement in the BRCA1 and BRCA2 genes does not seem like a major determinant of breast cancer susceptibility in the Korean population. A large-scale study needs to validate our result in Korea.

A retrospective prognostic evaluation analysis using the 8th edition of the American Joint Committee on Cancer staging system for breast cancer

PurposeBreast cancer is a group of diseases with different intrinsic molecular subtypes. However, anatomic staging alone is insufficient to determine prognosis. The present study analyzed the prognostic value of the American Joint Committee for Cancer (AJCC) 8th edition cancer staging system.MethodsThis retrospective, single-center study included breast cancer cases diagnosed from January 1999 to December 2008. We restaged patients based on the 8th edition AJCC cancer staging system and analyzed the prognostic value of the anatomic and prognostic staged groups. Follow-up data including disease-free survival (DFS), overall survival (OS), and clinic-pathological data were collected to analyze the differences between the two staging subgroups.ResultsThe study enrolled 7458 breast cancer patients with a 98.7-month median follow-up. Both the 5-year DFS and OS were significantly different between the anatomic and prognostic staged groups. The 5-year OS according to disease subtype was as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative [HR(+)/HER2(−)], 90.9%; HR(+)/HER2(+), 84.7%; HR(−)/HER2(+), 81.1%; and HR(−)/HER2(−), 80.9%. According to the anatomic stage, the 5-year OS of patients with stage III HR(+)/HER2(−) disease was superior to that of patients with stage II HR(−)/HER2(−) disease (88.3 vs. 86.5%). Per the prognostic stage, both the 5-year DFS and OS rates of patients with stage II HR(−)/HER2(−) disease were higher than those of patients with stage III HR(+)/HER2(−) disease (90.1 and 94.3% vs. 79.1 and 88.9%).ConclusionsThe prognostic staging system is a refined version of the anatomic staging system and encourages a more personalized approach to breast cancer treatment.

Novel cancer gene variants and gene fusions of triple-negative breast cancers (TNBCs) reveal their molecular diversity conserved in the patient-derived xenograft (PDX) model.

Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 patient-derived xenografts (PDXs) of TNBC. The overall success rate of PDX implantation was 45%, much higher than estrogen receptor (ER)-positive cases. Immunohistochemical analysis revealed conserved ER/PR/Her2 negativity (with two exceptions) between the original and PDX tumors. Genomic analysis of 10 primary tumor-PDX pairs with Ion AmpliSeq CCP revealed high degree of variant conservation (85.0%-96.9%) between primary and PDXs. Further analysis showed 44 rare variants with a predicted high impact in 36 genes including Trp53, Pten, Notch1, and Col1a1. Among them, we confirmed frequent Notch1 variant. Furthermore, RNA-seq analysis of 24 PDXs revealed 594 gene fusions, of which 163 were in-frame, including AZGP1-GJC3 and NF1-AARSD1. Finally, western blot analysis of oncogenic signaling proteins supporting molecular diversity of TNBC PDXs. Overall, our report provides a molecular basis for the usefulness of the TNBC PDX model in preclinical study.

Abstract P5-13-06: Concurrent gonadotropin-releasing hormone (GnRH) agonist administration with chemotherapy improves neoadjuvant chemotherapy responses in young premenopausal breast cancer patients

Background Gonadotropin-releasing hormone (GnRH) agonist therapy for ovarian function preservation shows promising results. This study aimed to determine the oncologic efficacy of GnRH agonist treatment concurrent with chemotherapy in a neoadjuvant setting. Patients and Methods A retrospective analysis was performed on 332 cases of invasive breast cancer in patients who were Results The median age was 32 ± 3.9 and 36 ± 3.0 years old in the GnRH agonist group and neochemotherapy-alone group, respectively (P Conclusion Concurrent administration of GnRH agonists during neoadjuvant chemotherapy improved pCR rates and suppressed Ki-67 expression especially in HR-negative tumors. Citation Format: Yoon TI, Kim HJ, Yu JH, Sohn G, Ko BS, Lee JW, Son BH, Ahn SH. Concurrent gonadotropin-releasing hormone (GnRH) agonist administration with chemotherapy improves neoadjuvant chemotherapy responses in young premenopausal breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-13-06.

Abstract P6-06-54: Analysis of treatment and survival of pathologic occult breast cancer with axillary lymph node metastasis: Nationwide retrospective study

Objective Occult breast cancer (OBC) is a rare presentation which accounts for 0.3-1.0% of all breast cancers. In spite of limited information, there is no consensus regarding the prognostic factors and treatment of OBC. This retrospective study intends to evaluate the overall survival and prognostic factors of occult breast cancer (OBC) in Korea. Method This study included 142 pathologic occult breast cancer patients from January 1990 to December 2009, identified from Korean Breast Cancer Society cancer registry. All patients had pathologically positive axillary lymph node (N1-N3) along with pathologically & radiologically negative in-breast lesion (T0/Tx) based on retrospective review of database. Among 142 patients, 32 patients had only axillary lymph node dissection (ALND), 56 patients had breast conserving operation (BCO) with ALND and 54 patients had mastectomy with ALND. 96 patients (96%) had N1 disease, 23 patients (16.2%) had N2 disease and 23 patients (16.2%) had N3 disease. Results There was no significant statistical difference in overall survival among different operation method, which is ALND only, BCO with ALND, mastectomy with ALND (p = 0.061), considering that 12 patients (37.5%) among 32 patients who only had ALND had N3 disease comparing that only 7 (12.5%) out of 56 patients and 4 (7.4%) out of 54 patients had N3 disease in BCO with ALND and mastectomy with ALND group separately. Univariate analysis revealed that only nodal status was significant prognostic factor (p = 0.0004), and other factors including radiotherapy (p = 0.696), chemotherapy (p = 0.302), estrogen receptor positivity (p = 0.144), progesterone receptor positivity (p = 0.254), total number of removed lymph node (p = 0.586) didn9t show statistical difference in overall survival. Conclusions This study suggests that OBC patients who only had ALND showed similar outcomes when comparing with patients who had BCO with ALND or mastectomy with ALND. Also only nodal status might be independent predictors for poor outcomes of occult breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-54.

Can We Skip Sentinel Lymph Node Biopsy in Patients Who Have Microinvasive Breast Cancer

Background: Sentinel lymph node(SLN) biopsy in patients with ductal carcinoma in situ(DCIS) was controversial. We may skip SLN biopsy when we performed conserving operation with small sized DCIS. But sometimes we can find DCIS with micro-invasive breast cancer (MIC) after operation. Should another operation be performed? We determined the incidence of positive axillary lymph node (ALNs) in patients with MIC, and the predictive factors of ALNs metastasis in these patients. Methods: Between July 1989 and January 2008, 9046 patients had operations performed on invasive breast cancers at Asan Medical Center. From July1989 to February 2003, ALND was performed to surgically stage the axilla. Since May 2003, SNB has been routinely performed for all cases. Patients who were treated with neoadjuvant chemotherapy and those who had no identifiable ALNs at surgery were excluded from the study. We retrospectively checked clinical and pathologic variables including diagnosis, patient demographics, size of DCIS, grade, multi-focal lesion, hormone receptor status, lymphatic invasion status etc. Results: 265 patients were identified with microinvasive (pathologic stage T1mic) breast cancer. Among these patients, 12 patients didn9t have ALN study. 2 patients had bilateral MIC. The research was conducted on the remaining 255 cases. There were 13 cases of ALN metastases identified in this group of patients(5%). Young age (p=0.006), multifocal lesion (p=0.040) and lymphatic invasion (p Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1019.